Studies are in progress to: 1. Characterize the neurotransmitter regulation of ACTH release and the level at which it occurs (CNS or pituitary), 2. Characterize the location within the CNS of CRF and its response to hypophysectomy, adrenalectomy, corticosteroid administration and surgical isolation of the hypothalamus, 3. Characterize the regulation of ACTH secretion (basal, circadian and stress induced) in the Brattleboro rat, 4. Investigate the nature of ACTH released (bioassay, immunoassay-antibodies directed to 1-39, and N- and C-terminals) in vivo in diseases affecting the human CNS-pituitary-adrenal axis, as well as under conditions of stress evoked release in both normal subjects and patients with pituitary and adrenal disease, 5. Investigate the control of ACTH release in patients with Nelson's Syndrome, and the efficacy of cyproheptadine and of somatostatin in reducing the elevated plasma ACTH levels present in this condition. BIBLIOGRAPHIC REFERENCES: Krieger, D.T., L. Amorosa, and F. Linick. Cyproheptadine Induced Remission in Cushing's Disease. New Engl J Med Vol. 293 (18) 893, 1975. Krieger, D.T., P.J. Howanitz, and A.G. Frantz. Absence of Nocturnal Elevation of Plasma Prolactin Concentration in Cushing's Disease, J Clin Endocrinol 42:260-272, 1976.